In the search for serum markers of hepatocellular cancer, several studies try to find a noninvasive marker for diagnosis of hepatocellular carcinoma (HCC) to facilitate the diagnosis and avoid the harmful complications of liver biopsy. Investigators have focused on Golgi protein 73 (GP73); also known as Golgi membrane protein 1 (Golm1) or Golgi Phosphoprotein 2 (Golph2) as non-invasive, available and inexpensive marker for the diagnosis of HCC. The present study aimed to evaluate the serum GP-73 mRNA expression as a marker for HCC diagnosis among Egyptian patients versus alpha fetoprotein. Subjects and Methods: The patients selected from the Hepatology, Gastroenterology and Infectious Diseases Department and from Gastroenterology and Hepatology Unit of Internal Medicine Department, Benha University Hospital. Subjects were classified into three groups: Group I : Included 20 apparently healthy subjects. Group II: Included 20 cirrhotic patients and not complicated by HCC, Group III: Included 40 patients diagnosed as liver cirrhosis complicated by HCC. The serum Golgi Protein 73 (GP73) mRNA was determined by semiquantitative RT-PCR. Results: GP-73mRNA was highly significant higher in HCC patients in comparison to cirrhotic and the control group (P < 0.001). ROC for AFP revealed that the best cut-off value is (>48ng/ml), at this point the sensitivity was 90 %, specificity was 90% and AUC was 0.96. However the ROC for GP-73mRNA expression revealed that the best cut-off value is (>5.11) at this point the sensitivity was 97.5%, specificity was 100% and AUC was 0.99. In conclusion, increased GP-73 mRNA expression could be associated with the presence of HCC and the serum Gp73 mRNA expression was more sensitive and more specific than AFP.